Trophoblast antigens in normal and abnormal human pregnancy.

With all of this information about trophoblast antigens, it is necessary to have a working hypothesis of how these antigens might be dealt with by a normal woman's immunologic system. Two sets of observations have helped formulate such a working hypothesis. First is the finding that trophoblast is the only normal tissue recognized by antibodies to TA1 (and it is exceedingly difficult to demonstrate maternal anti-TA1 in normal pregnancies). Second is the serologic result that antibodies to TLX antigens within the TA2 group are lymphocytotoxic (and maternal anti-TLX can be demonstrated both in normal and abnormal pregnancies). We interpret this as meaning that TA1 is "foreign" (i.e., oncoextraembryonic) antigen and TA2 (TLX) is "self"-antigen, and that mothers have TA2 (TLX) reactive B-lymphocytes in their repertoire. Antigen-reactive B-lymphocytes can be activated to produce TA1-blocking antibodies by either allotypic TA2 (TLX) in seminal plasma or allogeneic trophoblast membrane antigens during the host-versus-graft reaction subsequent to blastocyst implantation. If allotypic or allogeneic stimulation fails to produce an adequate anti-TA2 (TLX) response, the oncoextra-embryonic TA1 antigens are recognized and rapidly rejected. If allotypic or allogeneic stimulation produces an aberrant anti-TA2 (TLX) response (e.g., a cytotoxic rather than a blocking antibody), the extra-embryonic membranes and placenta come under immune attack and eventually are rejected. This working hypothesis has led us to develop new immunologic approaches to the diagnosis and prevention of some types of pregnancy failures in both mice and human beings.